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263 Cards in this Set

  • Front
  • Back
physiologic properties of the small intestine
Major site of digestion and absorption

Bile and pancreatic enzymes released

High surface area
physiologic properties of the large intestine
Last stages of digestion (bacteria)

Absorption of water, electrolytes, vitamins

Storage of waste products
what is the importance of nutrient/water/drug absorption?
Active transport
Solvent drag
what are absorption, secretion, and motility affected by?
Sympathetic/Parasympathetic NS
-->Central and enteric

Neurotransmitters: Serotonin, Opiate-like

Mechanical (distention/muscle contraction)
Defn of diarrhea
“alteration in a normal bowel movement characterized by an increase in the water content, volume or frequency (>3/day) of stool”
length of acute diarrhea
<72 hrs
self limiting
length of chronic/persistent diarrhea
>14-30 days
List clinical categories of diarrhea
exudative or inflammatory
altered inestinal motility(motor)
cause/type of infectious diarrhea
virus(flu, rotavirus, neurovirus)

cause/type of food intolerance diarrhea
lactose, gluten intolerance

cause/type of intestinal disorder diarrhea

inflammatory, motor, secretory
cause/type of endocrine diarrhea
diabetes, hyperthyroid

cause/type of pancreatic insufficiency diarrhea

Pt. pops to refer for diarrhea
Children (<3), elderly, immunosuppressed, pregnancy
Suspected invasive infection
Recent antibiotic use (superfinfection)
Diarrhea symptoms for referral
Presence of bloody, mucoid stools

Moderate to severe abdominal cramping

Fever > 101 F and/or protracted vomiting

Evidence of moderate to severe dehydration

> 5% of weight loss

Diarrhea >3 days
Types of antibiotic drug-induced diarrhea
infectious (c. difficile)


common examples: penicillin, macrolides, clindomycin
what percent of drug induced diarrhea cause by ABs?
what percent drug induced diarrhea caused by ADRs?
what is factitious diarrhea cause by?
such as
Senna, stool softener
Drug-induced diarrhea causes
Things to do to manage drug-induced diarrhea
thorough pt. hx
stop use of drug if possible
change drug to another
decrease dose(digoxin tox)
adjunctive tx w/ anti-diarrheal if pt. MUST be on the drug
components of thorough pt. hx for drug induced diarrhea
medical hx
recent AB use w/on 30 days after course is stopped
excessive use of sugar free products
rehydration for diarrhea
oral rehydration solns(ORS) = non-pharm

match output on hourly basis

smaller more freq. admin if pt. vomits
dietary modifiations for diarrhea
Avoid lactose (dairy products)
May need to interrupt feedings (kids)
Soup or salted crackers (adults)
“BRAT” (banana, rice, applesauce, toast) diet
2 key molecules for ORS, what do they do?

they transport accross the cell and allow reabsorption of water
Opioids and derivatives use to tx diarrhea

What do they do?
Loperamide(immodium AD) OTC


tincture of opium

*these drugs SLOW MOTILITY
adult tablet dose of loperamide

4 mg loading dose (2 tablets)
then 1 tablet after each loose stool (8 mg max/day OTC)

Rx max 16 mg/day
use for diphenoxylate/atropine (Lotomil)
severe diarrhea/unresponsive to loperamide

Rx narcotic/anticholinergi

slows motility

crosses BBB
use for tincture of opium
Slow ALL GI motility

ultrapotent, for SEVERE cases

Last line (after loperamide and Lotomil)
pharmacologic effects of Bismuth subsalicylate
COATING effect on stomach

ANTI-SECRETORY effects (insoluble complex forms)

BINDS TOXINS/microbes (Traveler's diarrhea)
adverse effects peptobismol
stool discoloration
Pepto Bismol CAUTION for use in these pts:
ASA allergy/intolerance
kids <12 yo (Reyes)
ACTIVE GI bleed (ulcer)
drug interactions with pepto bismol
antiplatelet effects (ASA, warfarin)

AB's (tetracycline-binding)
thyroid hormone (binding)
lactase role in diarrhea
enzyme for pts. w/ independent lactose intolerance

Replaces enzymatic deficiency

Lactaid® or Lactaid® Fast Act
-->Caplets or Chewable tablets (varying strengths)

Tablets taken at mealtimes with dairy products

Lactaid® lactose dairy products
probiotics role in diarrhea
Questionable benefit in routine treatment

May be role in antibiotic associated or radiation induced-diarrhea
Constipation defn
Relative to a patient’s normal frequency (3 times/day to 3 times/week may be considered “normal”)

Difficult evacuation of feces
-->Characterized by hard, dry stools
-->Incomplete evacuation
symptoms of constipation
**Decreased frequency of BM
-->relative to normal



Low back pain

Abdominal discomfort and distension

Incomplete evacuation
causes of constipation:
(drug, altered motility, neurogenic, endocrine, pregnancy, psycogenic, idiopathic, structural, dietary)
Drugs that cause Constipation

anti-histamine, anticholinergic

CCBs(non-DHPs), clonidine, diuretics

antacids(Ca, Al), sucralfate

Al, Ca, iron

TCAs, benzodiazepines
Referrals for constipation
Symptoms >1-2 weeks duration despite treatment

Bloody stool

Nausea, vomiting, bloating, cramping, fever

Decreased stool caliber


Abdominal distention

Unintentional Weight loss
drug INDICATIONS which cause Constipation
allergy/motion sickness
mineral supplement
Non-pharm treatment goals of constipation
treat underlying disorders
Ex: hypothyoridism

Dietery (increase fiber to 2-35 g/day, increase fluid intake)

criteria for selecting appropriate laxative products
Drug-drug interactions

Pregnancy or pediatric populations

Sugar content (diabetes)

Electrolyte content
(fluid/Na restricted: CKD, HF, Liver dx)
list bulk forming laxatives
polysaccharides (psyllium, inulin)

wheat dextrin

calcium polycarbophil (synth)

cellulose derivatives (synth.)
Polysaccharide bulk forming laxative characteritics
Soluble plant fiber

Psyllium (Metamucil)

Inulin Fiber (Metamucil Clear and Natural)

Some formulations contain gluten
polysaccharide laxative advantages
wide range of formulations (powder, wafers, tablet)
not absorbed
wheat dextrin laxative characteristics
Soluble fiber
Gluten free
Advantage: flavorless
May incorporate into regular food/drink/recipes
advantages to synthetic bulk forming laxatives
less potential for gas formation b/c synthetic, not plant derived
patient info for bulk forming laxatives
12-72 hrs for results

powders must be mixed w/ H2O

SE: bloating, gas
pts. to avoid bulk forming laxatives
suspected GI obstruction/ulceration

limited oral fluid intake: HF, liver dx
what are emollient laxatives?
anionic surfactants: AKA stool softener

used for prevention

docusate salts:
sodium: colace
calcium: surfak
inorder for docusate to be effective, what is the pt. criteria?
pt. must have adequate fluid intake
onset for emollient laxatives
24-72 hrs
role of emollient laxatives
prevention, chronic therapy
special populations for emollient laxatives
decrease straining: post-op, hemorrhoids, pregnant, post-pardum, HTN, post-MI
mech. of saline laxatives
examples of saline laxatives
magnesium citrate
magnesium hydroxide
sodium phosphate and sodium bisphosphate(Fleet)
indications for saline laxatives
immediate relief(severe constipation)
onset of action saline laxatives
oral: 3 hrs
enema: w/in 1 hrs
adverse effects of saline laxatives
abdominal cramping
electrolyte disturbances (Mg, Na, Phos)
relative contraindications for saline laxatives
renal failure
sodium restricted pts: HF, liver dx
children < 2 yo
FDA warning for saline laxatives:
oral sodium phosphate producte(Fleet, Osmoprep)
Acute Phosphate nephropathy
-->calcium phosphate crystals

Products should not be used for bowel cleansing
list osmotic laxatives
nonabsorbable sugars(lactulose, kristalose)
Glycerin information
onset w/in 5 mins-1 hr
often used for kids
Nonabsorbable sugars information
lactulose syrup Rx only
Kristalose (powder packet)
Onset :2-3 hrs

SE: gas formation
Polyethylene glycol information
osmotic laxative

Golytely bowel prep=NOW

Miralax (powder for susp.)=LATER(12-24 hrs)

Ok in pregnancy, Na//fluid restriction
Stimulant laxatives, what do they do?
Stimulates propulsive peristaltic activity

Local irritation of mucosa or by stimulation of the intramural nerve plexus

Work mostly in colon
indications for stimulant laxatives?
Constipation < 1 week or intermittent use

Prior to diagnostic procedures (in combo w/ osmotic lax)

Chronically for opiate induced constipation (with stool softener)
list stimulant laxatives
anthraquinones (Senna)

Senna dosing/onset
onset :8 hrs
often dosed at bedtime
Bisacodyl onset/dosing
6-12 hrs oral onset
1 hr suppository onset

do not crush enteric coated tablets b/c irritating
side effects of stimulant laxatives
electrolyte distrubances
melanosis coli (discoloration of GI tract)
stimulant laxatives, special populations
OK in fluid/Na restricted
AVOID in pregnancy
indication for Methylnaltrexone (Relistor)
treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient
methylnaltrexone admin
DNTK dosing
MOA Amitiza(lubiprostone)
Increases intestinal fluid secretion

Chloride channel activator (CIC-2)

May help with bloating and abdominal pain
Amitiza indication
Chronic idiopathic constipation in adults

IBS (constipation) in women 18 years or older
side effects of Amitiza
PI states women should have negative pregnancy test
Pt. Education for laxatives
Chronic use of laxatives only after provider evaluation

Proper use of desired formulation

Counseling on diet
--Evaluating sources of fiber

Reviewing current medications
What are the 2 types of IBD?
Ulcerative Colitis

Crohn's Dx
Pathophysiology of IBD
Exact etiology is unknown

Antigen-driven inflammatory response



Urban Dwellers


Infectious causes of IBD
genetic causes of IBD
family Hx(also risk factor)
environmental causes of IBD
smoking(Crohns worsens, UC gets better)
immunlogic causes of IBD
auto vs. nonauto
intestinal defect
abnormal defect
abnormal regulation of cytokines(TNF-alpha)
Features of UC
mucosal Dx
superficial inflammation, can also bleed
located exclusively in the colon
smooth inflammation
panctolitis/extensive colitis
UC dx affecting the majority of the colon, up to the splenic flexure
UC of the rectal area, most common site of UC
Features of Crohns Dx
penetrates much deeper than UC (through mucosa, muscle, to serosa)

pseudopolyps(noncancerous obstruction)

cobblestone/skip lesion pattern of inflammation(intermixed b/w normal and inflamed)

spans entire GI tract(mouth->rectum)

Terminal illeum most common location
clinical presentation UC
Rectal bleeding
Abdominal pain
clinical presentation of Crohns
Diarrhea (85%)
--Bloody stool ~ 50%
Crampy abdominal pain
Perianal lesions
Growth retardation in children (nutrient deficiency)
Weight loss
therapeutic goals for IBD
Induction and maintenance of remission
--Focus on inflammatory response
--Nutritional Support (Possibly TPN)
--Proper use of medications

Resolution of complications
--Drugs vs. Surgery
--UC is surgically curable

Alleviate systemic symptoms

Improve patient’s quality of life
List drug treatment classes for IBD
Adjuctive therapies(loperamide, antispasmodic, cholestyramine)





biologic response modifiers
Adjunctive therapies for IBD


use of loperamide in IBD
treat diarrhea
maybe useful in proctitis/diarrhea
use of antispasmodics,
treat abdominal pain and spasm
list antispasmodics in IBD tx
Dicyclomine (Bentyl)
Propantheline (pro-banthine)
hyoscyamine (Levsin)
use of cholestyramine in IBD
possibly for bile salt induced diarrhea following illeal resection (b/c large osmotic change from bile salt resbsorption)
complications of adjunctive therapies in IBD
Use anti-motility drugs with caution

May precipitate toxic megacolon

Surgical emergency

Stop anti-motility agents
How to choose IBD therapy?
1. Disease: UC vs. CD

2. Severity: mild-fulminant or in remission

3. Extent and location of disease

4. Pick drug(s) based on
Onset of action
Adverse effects
what are the 1st line tx for mild-moderate UC and CD?
MOA aminosalicylates
active component of aminosalicylates
5-ASA or mesalamine
what is necessary for mesalanine to be effective?
must be delivered to the site of action, has mostly topical effects (dont treat systemically)
features of sulfasalazine
diazo bond is cleaved by colonic bacteria

SOA: colon

5-ASA released and works topically
sulfapuridine carrier is absorbed and renally excreted(precipitates side effects)
how is mesalamine absorption prevented?
carrier molecule is added
sulfasalazine dosing/admin.
AVOID w/ sulfa allergy
generally performs better in CD compared to UC
enteric coated decrease dyspepsia
**Titrate when starting
sulfasalazine dose related adverse effects
GI Disturbance
--Folic acid supplementation (1mg)
sulfasalazine idiopathic adverse effects
Bone marrow suppression
Hemolytic anemia
decreased Sperm Production
what is the non-sulfa 5-ASA products?
mesalamine (formulations to prevent absorption: Asacol, Pentasa, Rowasa)

Olsalazine(2 5-ASA molecules, least used)

Balsalazide (non-sulfa, inert carrier molecule)

***These agents are preferred, and are all equal in efficacy
how to determine which aminosalicylate formulation to use
Based on the location of the dx:
Oral: SI, colon (all)
enema: up to splenic flexure(left sided dx)
suppository: rectal area(proctitis)
which non sulfa 5-ASA treats left sided dx?
which non sulfa 5-ASA treats proctitis?
which non sulfa 5-ASA is released in the small intestine and can treat Crohns dx?
which non sulfa 5-ASA are once daily dosing?
which non sulfa 5-ASA release in the colon and are similar to sulfasalazine?
5-ASA dosing:
Inducing remission may take 2-4 weeks

Topical agents superior for distal disease
-->Oral agents may be combined with topical for additive benefit (proctitis, Left sided dx)

Following remission reduce dose to maintenance
-->usually > 6 months, then may try stopping
-->Some patients may stay on 5-ASA indefinitely
Pt. education 5-ASA
Educate on proper use:
Enemas (suspensions)
Correct number of capsules/tablets

Do not crush or chew enteric coated or delayed release products
adverse effects of 5-ASA products
5-ASA products well tolerated

Headache, dyspepsia, anorexia

Olsalazine: 25% incidence of secretory diarrhea
use for corticosteroids in IBD
Reserved mostly for moderate or severe disease unresponsive to 5-ASA

Exception: Budesonide may be used first line in mild-moderate CD in patient with ileal disease

Topical (rectal) as initial therapy is not superior to topical 5-ASA

Systemic doses work faster than 5-ASA
Corticosteroid dosing
Patients with Moderate to Severe Disease
-->Systemic Oral
-----CD or UC
-----Budesonide: Crohn’s with ileal involvement
-->Topical: Proctitis or left sided disease
-->IV: hospitalized patients with severe disease

Typical course for acute flare is 5-10 days

No role in maintenance of remission
corticosteroid adverse effects
Adrenal suppression
Glucose intolerance
Aseptic necrosis
Impaired wound healing
what are the drugs of choice for fistula?
TNF-alpha inhibitors
What is Infliximab (remicade) indicated for?
Chimeric(mouse/human) monoclonal antibody vs. Tumor Necrosis Factor (TNF-α)

Indicated for UC and CD
--Moderate/Severe active disease (failed 5-ASA and corticosteroids)
--Very Effective for Fistulizing CD
--Maintenance of moderate/severe disease
features of Infliximab
Preferred to chronic use of steroids

Available as IV only (for active and maintenance tx)

Very expensive

Response ~ 40-80%

Patients may develop antibodies over time
-->Antibodies to infliximab (ATI)(neutralize, lose effectiveness)
what is Adalimumab (Humira) indicated for?
Recombinant IgG to TNF-α

Only indicated for moderate-severe CD
-->Not responsive to traditional treatments
--For patients losing response to infliximab
--Very expensive
what is Certolizumab(Cimizia) indicated for?
Crohns dx
Chimeric Fab’ vs. TNF-α
Some murine component
Role: Similar to infliximab
Patients with higher CRP (>10 mg/l) respond better
SubCut. injection, once monthly, all human
Adverse effects of biologics:
Infusion reactions (infliximab)
--infuse over >2 hours;
--Urticaria, decraese BP, CP, SOB, headache
--Related to ATIs

Injection site reactions
--Adalimumab, certolizumab

Delayed Hypersensitivity
--Usually 3-10 days after
--Fever, Rash, HA, sore throat, myalgia

--Bacterial (sepsis, URI, etc)
---->NEED BASELINE PPD to screen for TB
--Viral (Hepatitis B, Herpes)

Heart Failure (avoid in NYHA Class III/IV HF)

Lymphoma (small risk)

Lupus like syndrome (small risk)

**Pt. must be screened for hepatitis, TB
What is natalizumab (Tysabri) indicated for?
Humanized monoclonal antibody: α4-integrin inhibitor
--Interferes with leukocyte adhesion

Moderate-Severe CD after failure of other therapies
--Do not use with immunosuppressants or TNF α inhibitors
--Can only be prescribed through CD TOUCH® Program
black box warning for natalizumab?
Severe SE: progressive mulifocal leukoencephalopathy(PML)

*b/c of this, it is rarely used
last line option after TNF-alpha inhibitors fail
list the immune modulators (purine antagonists)
azathioprine (imuran)

6-mercaptopurine (Purinethol)
what do purine antagonists do? What are they indicated for?
anti-inflammatory effects
indicated for moderate-Severe UC or CD and/or steroid dependency
onset of action for purine antagonists
3-15 months
biggest downfall
adverse effects of purine antagonists/immune modulators
Check TPMT activity (before use)
Pancreatitis (azathioprine)
--3-15%, occurs usually within 6 weeks
Bone marrow suppression
--Monitor CBC
Hepatic dysfunction
methotrexate MOA
folate antagonist (inhibit dihydrofolate reductase)
what is methotrexate incidated for?
mod/severe Crohns dx
how is methotrexate dosed/admin?
once weekly dosing

Pregnancy cat. X
SEs of methotrexate
leukopenia, hypersensitivity pneumonitis, hepatic fibrosis, renal dysfunction, teratogenic
*lung/liver dysfunction very associated
*more side effects than azathioprine and 6-mercaptopurine
Treatment algorithm for moderate to severe UC
(top to bottom)
TNF-alpha blocker or immunomodulators
Treatment algorithm for mod/severe CD
(top to bottom)
TNF-alpha, immune modulators, methotrexate

fistulizing disease: TNF-alpha inhibitors
Antibiotic use in IBD
Adjunctive therapy in Crohns Dx
MOA antibiotics
interuption of bacterial role in inflammatory response
when to consider adding an antibiotic
Patients with mild-moderate CD not adequately responding to 5-ASA

Perineal disease/fistulas (OK + infliximab)

Colonic disease

Usually in combination with 5-ASA
antibiotics used in CD
ciprofloxacin (may combine w/ metronidazole)
side effects of metronidazole
peripheral neuropathy(long term use)

metallic taste

disulfiram reaction
side effects of cipro
drug interactions with Fe, Ca, Al, Mg
tendon rupture (long term)
List Other therapies for IBD
nictotine patches
what is cyclosporine used for
Used short-term for steroid refractory UC or Crohn’s and/or fistulizing Crohn’s disease

4mg/kg/day IV infusion

Minimally effective for oral maintenance
what are nicotine patches used for?
may try for patients with UC

Works better in ex-smokers
What is Cirrhosis?
•Represents pathologic changes to the liver including: fibrosis and collagen formation to replace normal tissue, distortion of hepatic vasculature leading to shunting of blood from hepatic inflow to outflow tracts, and impaired exchange between bloodstream and hepatocytes.
Increased intrahepatic circulatory resistance leads to portal vein hypertension and subsequent complications.
Vasodilation of peripheral blood vessels activates the sympathetic nervous system and the rennin-angiotensin-aldosterone-vasopressin-system to increase hydrostatic pressure.
what are the most common causes of cirrhosis in developed countries?
alcoholic liver disease
hepatitis c
risk factors for cirrhosis
regular alcohol consumption
>= 50 yo
diagnosis of cirrhosis
dependent on clinical signs and symptoms and incidental screening tests
what type of cancer can cirrhosis lead to?
hepatocellular carcinoma
What are the variables in the CPT(Child-Pugh-Turcotte) classification system?
total bilirubin
what are the classes and predictive life expectencies for the CPT?
Class A (5-6 pts) 15-20 yrs
Class B (7-9 pts) 4-14 yrs
class C (10-15 pts) 1-3 yrs
perioperative mortality for Class A-C in the PGT?
A 10%
B 30%
C 80%
Variables in the MELD (Model for end stage liver disease)

*the higher the score, the less likely to survive
whic classification system is used for basis of liver transplant?
cause of hypo-hyperglycemia
(BAD sign)
Altered glucose use and disturbed glucagon and insulin metabolism or activity
AST/ALT (↑ or ↔) cause
Inflamed and damaged hepatocytes
ALP/GGT (↑ or ↔) cause
Bilirubin (↑), unconjugated (or indirect) (↑) cause
Cholestasis and decreased excretion
Albumin (↓) cause
Diminished hepatic production, sequestration into ascites, and malnutrition
Prothrombin time or INR (↑) cause
Decreased hepatic production of factors V and VII and vitamin K deficiency
Immunoglobulins (↑, mainly IgG) cause
Shunting of portal blood carrying intestinal antigens to lymph tissues with resultant stimulation of plasma cells
Hyponatremia cause
Increased antidiuretic hormone activity
Anemia cause
Folate deficiency, hypersplenism, direct toxic effect of alcohol, and gastrointestinal blood loss
Thrombocytopenia and leukopenia cause
Hypersplenism, reduced hepatic thrombopoietin production
which lab manifestations are most likely sign that the pt. is getting worse?
LFTs decrease and INR increases
Jaundice, scleral icterus cause
Compromised hepatocyte excretory function
Spider angioma, palmer erythema cause
Vasodilation and increased estradiol due to decreased hepatic degradation
Nodular liver cause
Fibrosis and irregular regeneration
Splenomegaly cause
Portal hypertension and splenic congestion
Ascites cause
portal hypertension
Varices cause
portal hypertension
Caput medusae cause
Portal hypertension and reopening of umbilical vein
Epigastric valvular murmur (Cruveilhier-Baumgarten Syndrome) cause
Shunting of blood from portal vein to umbilical vein
White nails cause
Finger clubbing cause
Hypoxemia due to right-to-left shunting or portopulmonary hypertension
Gynecomastia, loss of male hair cause
Increased estradiol due to decreased hepatic degradation
Hypogonadism cause
Direct toxic effect of alcohol or iron
Encephalopathy cause
Ammonia accumulation, activation of central -aminobutyric acid, zinc deficiency, altered regulation of excitatory neurotransmitters, (N-methyl-D-aspartate, glutamine), and deposition of manganese in the basal ganglia
Asterixis cause
Hepatic encephalopathy, disinhibition of motor neurons
Foeter hepaticus (sweet pungent smell) cause
Volatile dimethylsulfide from portosystemic shunt
Anorexia, weight loss, fatigue, muscle wasting cause
Catabolic metabolism, anorexia
Hepatorenal syndrome cause
Splanchnic vasodilation leading to renal vasoconstriction via activation of the renin-angiotensin-aldosterone-vasopressin-system and sympathetic nervous system
Hepatopulmonary syndrome cause
Intrapulmonary vasodilation
Alcoholism prevalence/mortality
•Approximately 10 million alcoholics in the U.S.
•Fourth leading cause of mortality among men 25-64 years of age in the U.S.
•Accounts for 200,000 deaths/year and 12 billion dollars in medical costs/year.
list the 4 stages of alcohol induced cirrhosis
1. steatosis (fatty liver)
2. steatonecrosis(hepatitis)
3. Cirrhosis
4. hepatic failure
describe steatosis
AKA fatty liver
Fat accumulates in liver due to ethanol’s interference with normal cellular metabolism.
Little functional impairment and reversible at this stage
describe steatonecrosis
AKA hepatitis
Fat accumulation within hepatocytes leads to lysis and hepatocellular necrosis -->inflammation.
Immune mediated hepatic damage.
Reversal requires 3-8 months of abstinence.

(increase LFTs at this pt.)
describe cirrhosis (alcohol induced)
 Acetaldehyde stimulates the synthesis of collagen within parenchyma of liver.
 Fibrous tissue is deposited around terminal hepatic venules and hepatocytes to cause obstruction of hepatic flow and severe alterations of function.
Supportive treatment of cirrhosis
1.Abstinence from alcohol or treat hepatitis.
2.Discontinue hepatotoxic drugs.
3.Symptomatic treatment (GI discomfort).
4.Correct nutritional, mineral, and electrolyte deficiencies (iron, folate, thiamine, vitamin C, magnesium, potassium, phosphorus). Caution with vitamin A as it may worsen hepatotoxicity.
5.Manage glucose instability.
6.Maintain nutritional intake with moderate protein intake.
8.Coagulopathy: vitamin K replacement, Fresh frozen plasma, intravenous desmopressin (DDAVP), Exogenous factor VIIa
9.Portal hypertension and associated complications may be temporarily alleviated by insertion of transjugular intrahepatic portosystemic shunt (TIPS) but increased encephalopathy.
Prednisone treatment for cirrhosis
40-60 mg/day for 4-6 weeks to decrease inflammatory response of hepatitis but controversial (most effective if either very elevated serum bilirubin or encephalopathy is present).
Pentoxifylline treatment for cirrhosis
Pentoxifylline 400 mg tid x 4 weeks reduces short-term mortality and disease progression, likely due to reduced tumor necrosis factor (TNF) production.
Coagulopathy treatment options for cirrhosis
vitamin K replacement (10 mg/day) but limited effect

Fresh frozen plasma contains clotting factors with or without administration of platelets.

If uremia and thrombocyopneic, can try intravenous desmopressin (DDAVP) 0.4 mcg/kg.

Exogenous factor VIIa reverses coagulopathy in the short-term (but expensive).
List hepatic disorders due to portal hypertension
1. encephalopathy
2. variceal/gastric hemmorrhage
3. ascites
4. spontaneous bacterial peritonitis (SBP)
5. hepatorenal syndrome
Defn of encephalopathy
•A metabolic disorder of mentation, neuromuscular function, and consciousness associated with hepatic disease.
pathophysiology of encephalopathy
3 Main causes:
•Accumulation of unmetabolized ammonia(protein breakdown).
•Activation of central gamma-aminobutyric acid (GABA) by endogenous substances.
•Depletion of some excitatory neurotransmitters (N-methyl-D-aspartate) vs. accumulation of others (glutamate) cause intracellular water accumulation.

•Reduced activity of urea-cycle enzymes due to zinc deficiency and deposition of manganese in the basal ganglia.
Stage 0 encephalopathy symptoms
normal consciousness
normal personality
abnormalities only on psychologic analysis
Stage 1 encephalopathy symptoms
inverted sleep pattern, restless

forgetful, mild confusion, agitation, irritability

tremor, incoordination, impaired hand writing
Stage 2 encephalopathy symptoms
lethargy, slow responses

disorientation w/ regards to time, amnesia, decreased inhibitions, inappropriate behavior

ataxia, hypoactive reflexes
Stage 3 encephalopathy symptoms
somnolence, confusion

disorientation w/ regards to place, aggressive behavior

hyperactive reflexes, Babinski signs, muscle rigidity
Stage 4 encephalopathy symptoms

Precipitating factors for encephalopathy
• Gastrointestinal bleed, excess dietary protein, azotemia (diuretic-induced, renal failure), infection, constipation, metabolic/electrolyte disturbances (alkalosis, hypokalemia), drug-induced CNS depression.
Encephalopathy treatment
(consists of all of the following, but neomycin/metronidazole/rifaximin maybe reserved for > stage 3-4)
1. eliminate precipitating factors
2. protein restriction
3. lactulose
4. neomycin/ metronidazole/ rifaximin
5. IV mannitol if cerebral edema
how should protein be restricted in encephalopathy treatment?
<1 g/kg/day
or change to branch chain aa supplementation if grade 3-4
why should lactulose be used to treat encephalopathy?
Lactulose is degraded by colonic bacteria to lactic acid to decrease colonic pH to 5.5.
The acidic pH promotes conversion of ammonia to poorly absorbed ammonium ion.
Also acts as an osmotic laxative.
Administered orally as to maintain 2 stools/day.
Side effects include excessive diarrhea, abdominal distension, flatulence, and electrolyte abnormalities.
why are AB's used to treat encephalopathy?
Neomycin or metronidazole or rifaximin act by eliminating colonic bacteria which convert protein to ammonia.
Administer neomycin orally as 1-2 g qid; administer metronidazole orally as 500 mg bid-qid; administer rifaximin orally as 400 mg tid.
Side effects of neomycin include otitis dysfunction, renal failure, and diarrhea;
side effects of metronidazole include diarrhea, disulfiram reaction, peripheral neuropathy, and metallic taste;
side effects of rifaximin include diarrhea, nausea, vomiting
Defn. of Variceal(gastric) hemorrhage
•Azygous vein hemorrhage into the esophagus (or hemorrhage of other collateral veins into the stomach) due to hepatic cirrhosis and elevated portal vein pressure.
•At diagnosis of cirrhosis, approximately 55% of patients have varices.
•Annual risk of hemorrhage is 1-2% for no varices to 5-6% if large varices (≥ 5 mm).
Describe pathyphysiology of Variceal hemorrhage
• With liver cirrhosis / fibrosis, poor blood flow through liver combined with reduced hepatic production of vasoconstrictive substances (endothelins) and increased production of vasodilating substances (nitric oxide) causes pooling of blood in portal veinous system. This causes vasodilation of the hepatic artery and peripheral blood vessels which increases hepatic blood flow by local hepatic vasodilation and reflex tachycardia (to maintain blood pressure after peripheral vasodilation). The net result is increased portal vein pressure which increases collateral blood flow, including the azygous vein.
• Bleeding risk greatest when pressure gradient between the portal venous system and inferior vena cava is ≥ 12 mmHg.
(See diagram we drew on pg. 7 of the hepatic notes)
What happens during variceal hemorrhage
SVR increase
CO increase
HR increase (more blood gets backed up)
symptoms of variceal hemorrhage
•Spontaneous esophageal bleeding to cause vomiting of bright red blood and hypotension (shock).
Basic treatment for variceal hemorrhage
should always consist of a non-pharmacologic and either vasopressin, somatostatin, or octreotide (metoclopramide is optional)
Non-pharmacologic treatment for acute variceal hemorrhage
Treat hypovolemic shock with plasma expander or PRBCs
Prevent rebleeding with vitamin K, FFP or factor VIIa if prolonged INR and treat thrombocytopenia with platelets.
“Surgery” with balloon temponade, scleropathy, or band ligation. Band ligation most effective for controlling hemorrhage
Pharm treatment for acute variceal hemorrhage
Vasopressin (ADH) acts as a vasoconstrictor of capillaries and arterioles and reduces blood flow to the portal system to reduce portal hypertension and collateral blood flow. Administered as a 20 unit bolus followed by intravenous infusion of 24 units/hour. Side effects include fluid retention, hypertension, coronary vasoconstriction, reduced cardiac output, myocardial infarction, and arrhythmias. Therefore, often administered with intravenous nitroglycerin 40 microg/minute. OR
Somatostatin inhibits the release of vasodilatory gastrointestinal peptides such as glucagon, calcitonin, vasoactive intestinal polypeptide, and substance P to subsequently reduce splanchnic and mesenteric blood flow and reduce portal hypertension. Administered as a 500 unit bolus followed by intravenous infusion of 250 units/hour for 3-5 days. Side effects include nausea, vomiting, hyperglycemia, hypocalcemia, headache, thrombocytopenia. OR
Octreotide acts like somatostatin but also reduces azygous blood flow. Administered as a 50 unit bolus followed by intravenous infusion of 25 units/hour for 3-5 days. Side effects include diarrhea, nausea, vomiting, headache, dizziness, hypoglycemia
Metoclopramide (theoretical, optional) acts by reducing azygous blood flow. Administered orally or intravenous as 20 mg x1. Side effects include diarrhea, abdominal cramping, reduced urine output, and extrapyramidal CNS effects
Non-pharm prevention for variceal hemorrhage
Transjugular intrahepatic portosystemic shunt (TIPS).
--->May increase encephalopathy
Pharm prevention for variceal hemorrhage
ALL pts. should be on non-selective beta blocker to prevent rebleeds
Nonselective beta blockers (propranolol or nadolol) act by inhibiting beta-2 adrenergic receptors to produce vasoconstriction of capillaries and arterioles and reduces blood flow to the portal system to reduce portal hypertension and collateral blood flow; and by inhibiting beta-1 adrenergic receptors to decrease cardiac output and reduce blood flow to the mesenteric vascular system. Administered orally as 20 mg qday and titrated to a heart rate of 55-60 bpm or 25% reduction.
Oral nitrates may be substituted or added to beta blocker if patient intolerant or not responding to beta blocker.
side effects of non-selective beta-blockers
nausea, vomiting, diarrhea, hypotension, hyperglycemia, electrolyte disturbances, bronchospasm, heart failure, sexual dysfunction (males), nightmares. Propranolol - hepatically eliminated vs. nadolol - renally eliminated
side effects of vasopressin
fluid retention, hypertension, coronary vasoconstriction, reduced cardiac output, myocardial infarction, and arrhythmias
side effects of somatostatin
nausea, vomiting, hyperglycemia, hypocalcemia, headache, thrombocytopenia
side effects of octreotide
diarrhea, nausea, vomiting, headache, dizziness, hypoglycemia
what does vasopressin do in treating variceal hemorrhage?
Vasopressin (ADH) acts as a vasoconstrictor of capillaries and arterioles and reduces blood flow to the portal system to reduce portal hypertension and collateral blood flow. Administered as a 20 unit bolus followed by intravenous infusion of 24 units/hour.
what does somatostatin do in treating variceal hemorrhage?
Somatostatin inhibits the release of vasodilatory gastrointestinal peptides such as glucagon, calcitonin, vasoactive intestinal polypeptide, and substance P to subsequently reduce splanchnic and mesenteric blood flow and reduce portal hypertension. Administered as a 500 unit bolus followed by intravenous infusion of 250 units/hour for 3-5 days
What dos octreotide do in treatment of variceal hemorrhage?
Octreotide acts like somatostatin but also reduces azygous blood flow. Administered as a 50 unit bolus followed by intravenous infusion of 25 units/hour for 3-5 days
Defn ascites
•Collection of free fluid within the peritoneal space.
•Most common complication of portal hypertension occurring in 50% of patients over 10 years with mortality rate of 50% at two years.
•Stage I = detectable by ultrasound, Stage II = moderate volume and distension, Stage III = large volume and marked distension, Stage IV = refractory to diuretic therapy
Describe pathophysiology of ascites
•Low serum oncotic pressure due to hypoalbuminemia, local vasodilation with impaired endothelium, and elevated hydrostatic pressure due to increased splanchnic blood flow and portal hypertension after sodium/water retention from vasodilation forces fluid into peritoneal cavity.
•Peritoneal fluid only collects when pressure gradient between the portal venous system and inferior vena cava is ≥ 12 mmHg
Describe Ascites flow chart
(top to bottom)
Liver Failure leads to:
increase SVR
increase RAAS
increase Fluid
increase Hydrostatic P
=>leak fluid into peritoneal cavity=>ascites

Liver Failure also leads to:
decrease Albumin
decrease Oncotic P
=>leak fluid into peritoneal cavity=>ascites
Symptoms of ascites
•Extended belly, fluid wave, edema, respiratory difficulties, hyponatremia, hypoalbuminemia, hepatorenal syndrome
Basic treatment outline for ascites
bed rest
sodium/fluid restriction
paracentesis (abd. fluid tap)
how much should sodium be restricted in ascites
how much should fluid be restricted in ascites
1-2 liters/day
Goal of water removal with ascites (w/ and w/out peripheral edema)
0.5 kg/day w/out peripheral edema
2 kg/day with peripheral edema
which diuretics are used to treat ascites?
how does spironolactone treat ascites?
Side effects?
Spironolactone acts by inhibiting aldosterone which is elevated in liver failure. Administered orally as 100 mg qday to a maximum of 400 mg qday. Side effects include gynecomastia, nausea, vomiting, cramping, diarrhea, gastric bleed, drowsiness, lethargy, headache, rash, decreased libido, irregular menses, hyperkalemia, polyuria
how does furosemide treat ascites?
Side Effects?
Furosemide acts as a loop diuretic. Administered orally or intravenous as 40 mg qday to a maximum of 160 mg qday. Side effects include electrolyte disturbances, diarrhea, nausea, dizziness, weakness, polyuria, rash, tinnitus
what is paracentesis used for in ascites?
Used if failure to other therapies and relief of abdominal pain or respiratory difficulties.
Complications include perforation, hemorrhage, shock, and infection
how is albumin used for ascites treatment?
Acts by pulling ascitic fluid into the vascular system and often used in combination with paracentesis. Effects are not long lasting. Intravenous administration as 25-50 g qday. May prevent renal dysfunction when ascites is present
Defn Spontaneous bacterial Peritonitis (SBP)
•Infection of the ascitic fluid due to E. coli (70%) > Klebsiella species (10%) > Strept. pneumoniae.
•Lifetime risk in patients with cirrhosis is 33% with annual rate of 7-30%.
pathophysiology of SBP
•Bacterial translocation from gut to lymph to ascitic fluid due to impaired gut contraction, mucosal damage of gut, reduced ascitic protein, impaired activity of the reticuloendothelial system, and reduced ascitic compliment
symptoms of SBP
•Ascites, hyperthermia, abdominal pain, renal dysfunction, encephalopathy, hyponatremia; ascitic fluid with bacteria, serum albumin – ascitic albumin > 1.1 g/dL, and > 250 PMNs/mm3
Prophylaxis of SBP
Patients with cirrhosis and either acute ascites or gastrointestinal hemorrhage require antibiotic prophylaxis (quinolone, TMP/SMX, amoxicillin/clavunaic acid), usually for 7-10 days unless prior history of SBP then life long but modified dose (e.g. three times weekly). This reduces incidence of SBP and may improve mortality
basic treatment for SBP
antibiotics for 7-10 days (ceftriaxone most common)
How to give albumin to treat SBP?
Albumin as 1.5 g/kg at diagnosis and 1 g/kg three days later reduces the incidences of renal impairment and mortality
Defn hepatorenal syndrome (HRS)
•Renal vasoconstriction and progressive renal dysfunction in the absence of structural kidney damage.
•Incidence is 10% in cirrhotic patients and 20% if ascites is present.
•Type 1 progresses over weeks and type 2 occurs over months.
•Diagnosis requires exclusion of other causes
Pathophysiology of HRS
Splanchnic vasodilation leading to activation of renin-angiotensin-aldosterone-vasopressin-system and sympathetic nervous system and subsequent renal vasoconstriction
symptoms of HRS
Rapidly progressive renal failure.
Basic treatment for HRS
discontinue diuretics and nephrotoxic angents
How do vasoconstrictors work to treat HRS?
Theory is to vasoconstrict splanchnic vasculature to reverse local vasodilation mitigate the activation of the renin-angiotensin-aldosterone-vasopressin-system and sympathetic nervous system. Side effects include ischemic events.
Intravenous vasopressin 0.04-0.4 units/minute OR subcutaneous octreotide 100-200 units tid with oral midodrine 10 mg tid
Defn Wernicke-Korsakoff Syndrome
Wernicke’s encephalopathy is a severe neurologic disorder caused by thiamine deficiency
Symptoms of Wernicke-korsakoff Syndrome
Classic triad of Wernicke’s encephalopathy: mental status changes, ambulatory difficulties, ocular problems. Korsakoff’s psychosis is an irreversible disorder among patients surviving Wernicke’s encephalopathy
Prevention/treatment of Wernicke-korsakoff syndrome
Thiamine 50-100 mg po/im/iv daily for 3 days as prevention. Extend to 3 weeks if treatment
Defn Alcohol W/drawal Syndrome
Acute abstinence of alcohol to cause a collection of symptoms
describe stage 1 of Alcohol W/drawal
Stage I: Begins 6-8 hours after ethanol concentrations decline. Symptoms include tremors, anxiety, agitation, hypertension, tachycardia, diaphoresis, fever, diarrhea, cramping, insomnia
Describe stage 2 of alcohol w/drawal
Stage II: Begins within 24 hours and may last 1-3 days. Symptoms include visual or auditory hallucinations, tremors, anxiety, agitation, hypertension, tachycardia, diaphoresis, fever, diarrhea, cramping, insomnia
Describe stage 3 of alcohol w/drawal
Stage III: Begins within 72 hours. Symptoms as per stage II but includes seizures
Describe stage 4 of alcohol w/drawal
Stage IV: Delirium tremens (DTs) occur 3-5 days after cessation of drinking. Symptoms include confusion, hallucinations, psychosis, combativeness, hypertension, tachycardia, diaphoresis, fever. Mortality as high as 25%
Basic treatment options for alcohol w/drawal
Usually only a benzodiazepine is needed
Beta-blockers or clonidine
alcohol (to prevent w/drawal)
why are benzodiazepines used for alcohol w/drawal
Benzodiazepines are the agents of choice for prevention and treatment of withdrawal symptoms. All have equiefficacy but specific agent of choice is controversial. Lorazepam only undergoes phase two metabolism and thus is less likely to be affected by liver dysfunction but chlordiazepoxide, diazepam, and clonazepate are longer acting and may provide the convenience of self taper. Doses are usually initiated as needed until symptoms are controlled and then administered every 4-6 hours as a scheduled regimen that is gradually tapered over 5-7 days. Many alcohol withdrawal scales exist to guide administration of benzodiazepine
why is haloperidol used to treat alcohol w/drawal?
Haloperidol (2-10 mg every 4-6 hours) may be helpful for the control of hallucinations or agitation, especially if high dose benzodiazepines are not adequately controlling symptoms
why are betablockers/clonidine used to treat alcohol w/drawal
Beta-blockers or clonidine may help control sympathetic hyperactivity
why is phenytoin used to treat alcohol w/drawal?
Phenytoin occasionally administered prophylactically to patients with history of withdrawal seizures but studies suggest that phenytoin is no better than placebo. Benzodiazepine administration is probably all that is needed to prevent seizures